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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 361 records · Page 20Linked to original sources

Hepatic metastasis detection: comparison of three CT contrast enhancement methods.

A prospective, blinded comparison of three methods of hepatic contrast enhancement in computed tomography (CT) was conducted in 15 patients with colorectal carcinoma metastatic to the liver. Arterial portography (AP-CT) was performed with injection of contrast material into the superior mesenteric artery during CT. Delayed scanning (DS-CT) was performed 4 hours after intravascular administration of contrast material (mean dose, 280 mL). CT with an ethiodized oil emulsion (EOE-CT) was performed 1 hour after slow intravenous infusion of the emulsion. All patients underwent laparotomy following imaging studies. A lesion-by-lesion analysis of 56 metastases showed no significant differences in sensitivity (AP-CT, 77%; DS-CT, 83%; EOE-CT, 82%), but the false-positive rate for AP-CT was significantly higher than that for DS-CT (P less than .001) or EOE-CT (P less than .01). False-positive rates for EOE-CT and DS-CT were not significantly different. The predictive value of a positive test was 63% for AP-CT, 90% for DS-CT, and 81% for EOE-CT. AP-CT does not appear to be clinically useful for detection of hepatic metastases because of the high false-positive rate. No difference could be demonstrated between DS-CT and EOE-CT. DS-CT is a valuable method for hepatic contrast enhancement.

Adult↗

Food restriction and recovery of nonabsorbed indicators from the small intestine of the rat.

Indicators of net water movement are used in a variety of intestinal transport studies. Such indicators should be virtually unabsorbed under study conditions. The effects of stimuli that alter intestinal mass on indicator recovery have not been examined. We used the male albino rat to study the effects of food restriction (50%) and fasting on recovery of indicators perfused intraluminally through the entire small intestine. Recovery of PEG 4000 and phenol red was essentially complete (98-100%) from control and restricted groups, but was 96% from the fasted group. PEG 400, consisting of a homologous series of polymers of which seven were measured (MW 242-506), was also perfused. The lower-molecular-weight polymers were absorbed. Absorption decreased with increasing molecular weight, and the slope of the relation of absorption to molecular weight was the same for all groups.

Animals↗

Ultrasonically activated gas-filled micropores release hemoglobin and antigens from human erythrocytes in vitro.

Antigen release from human type B red blood cells was investigated by sensitive capillary-tube assay techniques after subjecting 3% suspensions to a controlled form of ultrasonic cavitation. Cells were kept suspended during the 1,000-sec exposures by an orbital motion of the sample chamber. Several spatial peak intensities of continuous 1.7 MHz ultrasound were applied to the samples which included gas-filled 4-microns diameter micropores in hydrophobic membranes. Free hemoglobin, indicating hemolysis, and free antigenic material, indicating solubilization of antigens, were found in the supernates of suspensions exposed to 90 mW/cm2 or 180 mW/cm2, respectively, or greater intensities. None of the free antigenic material could be attributed to antigen loss by surviving cells. For these conditions, the antigen release effect of ultrasound appears to be a byproduct of cavitation-induced cell lysis.

ABO Blood-Group System↗

Mitochondrial DNA of two independent oligomycin-resistant Chinese hamster ovary cell lines contains a single nucleotide change in the ATPase 6 gene.

We have determined the nucleotide sequence of the URF A6L and ATPase 6 genes of the mitochondrial DNA of wild-type Chinese hamster ovary (CHO) cells and of two independently isolated, cytoplasmically inherited CHO mutant cell lines that are resistant to oligomycin, an inhibitor of the mitochondrial ATP synthase (ATPase) complex. Comparison of the nucleotide sequences of the mutants with that of their parental cell line revealed a single nucleotide difference, a G-to-A transition at nucleotide 433 of the ATPase 6 gene. This single base pair change predicts a nonconservative amino acid change, with a glutamic acid residue being replaced by a lysine residue at amino acid 145 of the ATPase 6 gene product in the mutants. This glutamic acid residue and several others in the surrounding amino acid sequence are conserved among all species examined to date. Analyses of several of the biochemical properties of the oligomycin-resistant CHO mutants indicate that the glutamic acid residue at position 145 of subunit 6 of the mitochondrial ATP synthase complex is important for the binding of oligomycin to the enzyme complex, but is not essential for proton translocation.

Adenosine Triphosphatases↗

Haemolysis in vivo by therapeutic intensities of ultrasound.

Therapeutic intensities of MHz ultrasound directed at the upper abdominal area of rats in vivo resulted in damage to the circulating red blood cells. This damage was detected as free haemoglobin in the plasma as well as microspheres and spherocytic cell fragments which are characteristically produced when blood is heated to more than 49 degrees C. The magnitude of this effect increased with increasing frequency of the ultrasound and was dependent upon the time-averaged intensity, even when the ultrasound was delivered as bursts of high spatial peak intensities. Thermal lesions were found above 10 W/cm2 SP at 1 MHz and above 3 W/cm2 SP at 3.4 MHz. These results show that the observed blood cell damage is primarily a thermal effect which occurs as the blood perfuses anatomical structures which are being heated by the ultrasound beam.

Animals↗

Lack of effect of pulsed ultrasound on ABO antigens of human erythrocytes in vitro.

The efficacy of pulsed ultrasound in removing ABO blood group antigens from human erythrocytes was investigated in vitro. Cell suspensions were exposed to 5.25 MHz focused ultrasound with 1.23 microseconds pulses, at 0, 20, and 37 degrees C using spatial peak, pulse average intensities of 11, 126, and 1000 W/cm2 and pulse spacings of 10, 100, and 1000 microseconds. A second experiment involved application of 7.5 MHz pulses of 0.77 microseconds duration and 8 W/cm2 SPPA intensity which were spaced 1.25 ms apart. Exposed cells were tested for agglutination by antibody to determine changes in antigen expression. In addition, supernates from exposed cells were tested for the presence of soluble antigen. A sensitive capillary tube agglutination technique was developed for these experiments. No detectable antigen removal occurred as a result of any of the pulsed ultrasound exposures as compared to sham exposures. A positive control, which employed antigenic material prepared from cells disrupted by ultrasonic cavitation, indicated that the assay could detect the soluble antigen equivalent of about one cell in 10,000.

ABO Blood-Group System↗

Ultrasonically induced intravascular streaming and thrombus formation adjacent to a micropipette.

Ultrasonically induced microstreaming around bubbles of gas have been shown to cause damage to biological materials in vitro at clinical exposure levels. The potential for ultrasonically induced cavitation and microstreaming in mammalian systems is of interest with respect to the safe application of clinical ultrasound. Ultrasonically induced intravascular microstreaming and formation of thrombi at 1 MHz is demonstrated adjacent the tip of a micropipette in contact with a mesenteric vessel of the mouse. These effects occur at or above therapeutic levels.

Animals↗

Comparison of hot contrast material and hot saline for renal ablation in a canine model.

Renal ablation was performed in eight dogs with either 76% diatrizoate for normal saline. Both fluids were heated to 100 degrees C before injection. Coagulation necrosis and tubular atrophy were seen with both agents, indicating that much of the effectiveness of hot contrast material is due to heat. Diatrizoate also caused glomerular sclerosis, probably due to its inherent nephrotoxicity. Hot diatrizoate is probably more effective for renal ablation, but may not have an advantage over hot normal saline outside the kidney. Because of the risk of infection, prophylactic antibiotics are advised when renal ablation is performed with hot fluids.

Animals↗

Intestinal calcium transport in the spontaneously hypertensive rat: response to calcium depletion.

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.

Animals↗

Vascular imaging with MRI: inadequacy in Takayasu's arteritis compared with angiography.

Magnetic resonance imaging (MRI) and angiography were compared in a prospective and blinded fashion in 10 consecutive patients with Takayasu's arteritis to evaluate the ability of MRI to detect vascular abnormalities in the large arteries of the thorax and abdomen. Only the aorta and its major branches were studied. MRI was performed with a 0.5-T superconducting instrument and a body coil. Overlapping cuts, oblique views, and cardiac gating were used. Using angiography as the gold standard, MRI correctly identified all lesions in three patients, gave false-positive findings in two patients, and gave false-negative findings in five patients. In the latter five patients, MRI missed areas of major pathology in proximal arch vessels. MRI sensitivity was only 38% with a patient-by-patient analysis and 54% with a lesion-by-lesion analysis. The visualization of specific arteries with MRI was compared to visualization with angiography, and was markedly inferior in all vessels except the aorta, the innominate artery, and the common iliac arteries. It appears that with current equipment and technology, MRI is inadequate as a screening examination or for detailed evaluation of arterial disease other than the aorta except in highly selected cases.

Adolescent↗

Selective venous sampling for gastrin to localize gastrinomas. A prospective assessment.

In 27 consecutive patients with Zollinger-Ellison syndrome, we prospectively evaluated the ability of selective venous sampling for gastrin to localize gastrinomas, then compared the results with those from imaging studies and with findings at surgery. All patients had a gastrin gradient, but in only 20 patients was it significant. Neither the magnitude of the gastrin gradient nor its presence or absence correlated with the frequency with which gastrinoma was found at surgery. A gastrinoma was found at surgery in 15 patients, of whom 12 had positive imaging studies, 11 had a significant gastrin gradient, 14 had both tests positive, and 1 had both tests negative. A gastrinoma was not found at surgery in 12 patients, of whom 8 had a significant gradient and none had a positive imaging study. Gastrin sampling has equal sensitivity with imaging studies in localizing gastrinoma, but imaging studies have higher positive and negative predictive values and higher specificity. Thus, selective venous sampling for gastrin is much less useful in localizing gastrinoma than has been suggested and should not be routinely done preoperatively in patients with Zollinger-Ellison syndrome.

Adult↗

Thermal and heart rate response to ultrasonic exposure in the second and third trimester dog fetus.

A total of 39 fetuses from five pregnant dogs were used in this study. Following pentobarbital anesthesia of the dams the gravid uterus was exposed and partially exteriorized. Fetal and maternal electrocardiograms were recorded, along with fetal abdominal temperatures, during ultrasound exposures of 3.4 MHz and 2, 4, 6, 8 or 12 W/cm2 (continuous wave), spatial average intensities, for 6 minutes. Baseline fetal abdominal temperatures were 35.2 +/- 1.5 (SD) degrees C. Baseline fetal heart rates were 176.8 +/- 4.3 (SD) beats per minute. These studies indicate that the product of intensity and time of exposure, under the conditions of these experiments, is directly related to increases in fetal abdominal temperature and fetal heart rate.

Animals↗

A study of the kinetic mechanism of elongation factor Ts.

Elongation factor Ts (EF-Ts) catalyzes the reaction EF-Tu X GDP + nucleotide diphosphate (NDP) reversible EF-Tu X NDP + GDP where NDP is GDP, IDP, GTP, or GMP X PCP. The EF-Ts-catalyzed exchange rates were measured at a series of concentrations of EF-Tu X [3H] GDP and free nucleotide. Plotting the rate data according to the Hanes method produced a series of lines intersecting on the ordinate, a characteristic of substituted enzyme mechanisms. GDP is a competitive inhibitor of IDP exchange, a result predicted for the substituted enzyme mechanism but inconsistent with ternary complex mechanisms that involve an intermediate complex containing EF-Ts and both substrates. The exchange of both GTP and the GTP analog GMP X PCP also follow the substituted enzyme mechanism. The maximal rates of exchange of GDP and GTP are the same, which indicates that the rates of dissociation of EF-Ts from EF-Tu X GDP and EF-Tu X GTP are the same. The steady-state maximal exchange rate is slower by a factor of 20 than the previously reported rate of dissociation of GDP from EF-Ts X EF-Tu. This is interpreted to mean that the rate-determining step in the exchange reaction is the dissociation of EF-Ts from EF-Tu X GDP.

Guanosine Diphosphate↗